Conversion of in Vitro Fertilization Cycles to Intrauterine Inseminations in Patients With a Poor Ovarian Response to Stimulation

Not Applicable

Completed

• Conditions: Infertility
• Interventions: Procedure: IVF / IVF-ICSI; Procedure: IUI

• Registration Number: NCT03362489
• Lead Sponsor: University Hospital, Angers

Brief Summary

The purpose of this study is to compare the efficiency of conversion to IUI and IVF in patients with a poor ovarian response to stimulation

Detailed Description

In 5 to 10% of in vitro fertilization (IVF) cycles, a poor response to ovarian stimulation (defined as less than 4 mature follicles) is noted, even though high doses of exogenous gonadotropins are used. To date, there is no consensus on the ideal management strategy in poor responders. There are three therapeutic options available nowadays:

1. Oocyte retrieval is performed and the IVF cycle continued, despite the low number of mature follicles.

2. Conversion of the IVF cycle to an intrauterine insemination (IUI), on the condition of having at least one patent fallopian tube and good semen parameters.

3. Cancelation of the IVF cycle. In everyday practice, it is difficult for the physician to cancel the IVF cycle in the presence of 2, 3 or 4 mature follicles, especially following a lengthy stimulation.

If live birth rates were comparable between IUI and IVF, conversion to IUI would be the better option for poor responders, since it would avoid an invasive procedure (oocyte retrieval) and the associated risk of complications, and is associated with at a lower cost.

To our knowledge, no prospective randomized controlled trial comparing IVF to conversion to IUI in poor responders has been published to date. The studies published so far have been retrospective and observational, and had several methodological flaws.

Therefore, we aimed to analyze whether conversion of IVF cycles to IUI in poor responders would result in the same live birth rates as oocyte retrievals followed by embryo transfers.

Study Timeline

• Study First Submitted: 2017-11-24
• Study First Submitted QC: 2017-12-04
• Study First Posted: 2017-12-05
• Study Start: 2018-01-10
• Primary Completion: 2022-11-25
• Study Completion: 2024-03-14
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-17
• Last Update Posted: 2024-06-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 462

Inclusion Criteria

• Patients who accepted being included and signed the consent forms.

• Age ≥18 years et <43 years.

• IVF cycle with and without Intra Cytoplasmic Sperm Injection (ICSI):

  • "Conventional" Agonist (long and short) or antagonist protocol, using urinary or recombinant gonadotropins.
  • Having only 2, 3 or 4 mature follicles (≥14 mm) on ovulation trigger day.

Exclusion Criteria

• Confirmed bilateral tubal occlusion

• Non-French speaking patients

• Partners with severe oligoasthenoteratospermia (OATS) (<5 millions motile spermatozoa in the ejaculate)

• Suboptimal stimulation protocols:

  • Protocols ≤ 150 IU of daily gonadotropins
  • Mild stimulation protocols
  • Natural and modified natural cycle protocols

• Women under legal guardianship

• Women with no health or social security coverage

• Women participating in other interventional trials

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IVF / IVF-ICSI	IVF / IVF-ICSI	In Vitro Fertilization / In Vitro Fertilization - Intracytoplasmic Sperm Injection (ICSI)
IUI	IUI	Intrauterine insemination

Primary Outcome Measures

Name	Time	Method
The main criterion is the live birth rate	12 months	Defined as the birth of a living infant after 22 weeks gestational age (GA), or weighing ≥ 500 g.

Secondary Outcome Measures

Name	Time	Method
Biochemical pregnancy rate	5 Weeks	Defined as serum HCG levels \>10 IU/L, 14 days after the IUI or the embryo transfer, followed by a rapid decrease until being undetectable.
Clinical pregnancy rate	6-7 Weeks	Defined as fetal cardiac activity at 6-7 weeks GA
Spontaneous pregnancy loss (PL) rate	12 Weeks	Including early and late pregnancy losses
Multiple pregnancy rate	7-8 Weeks	Defined as more than two embryos visualized on ultrasound at 7 weeks GA.
Term at delivery	12 Months	Term at delivery in Gestational age (GA)
Neonatal complications	12 Months	Neonatal complications
Neonatal survival	12 Months	Neonatal survival
All outcome measure will be further analyzed according to the number of follicles on trigger day (2, 3 or 4) and patients' age (<40 years vs. ≥40 years)	12 Months	Assess the impact of conversion to IUI, compared to IVF, on overall outcomes in in women with a poor ovarian response to stimulation, according to the number of follicles on trigger day (2, 3 or 4) and patients' age (\<40 years vs. ≥40 years)
All outcome measures will be further analyzed in the subgroup of women considered poor responders according to the Bologna criteria	12 Months	Assess the clinical efficiency of conversion to IUI, compared to IVF, in women considered "poor ovarian responders" according to the Bologna criteria
The rate of IVF cycles with empty follicle syndrome and no embryo transfers.	1 Week	Analyze the rate of IVF cycles with empty follicle syndrome and no embryo transfers
Cumulative clinical pregnancy and live birth rates in the IVF group, thus taking into account fresh and frozen embryos transferred in subsequent cycles	12 Months	Assess the impact of conversion to IUI, compared to IVF, on the cumulative clinical pregnancy and live birth rates - taking into account frozen embryo transfers in IVF - in women with a poor ovarian response to stimulation
Cost-efficiency analysis at 12 months	12 Months	Compare the cost-efficiency of both strategies at 12 months

Trial Locations

Locations (32)

Polyclinique Jean Villar; 🇫🇷 Bruges, France

Victor Pauchet Clinic; 🇫🇷 Amiens, France

UH Caen; 🇫🇷 Caen, France

UH Besançon; 🇫🇷 Besançon, France

Jean Verdier Hospital, APHP; 🇫🇷 Bondy, France

Clinique Léonard de Vinci; 🇫🇷 Chambray-lès-Tours, France

Cholet Hospital; 🇫🇷 Cholet, France

Antoine Béclère Hospital AP-HP; 🇫🇷 Clamart, France

Sud Francilien Hospital; 🇫🇷 Corbeil-Essonnes, France

IHC Créteil; 🇫🇷 Créteil, France

Tertre Rouge Clinic; 🇫🇷 Le Mans, France

UH Grenoble; 🇫🇷 Grenoble, France

UH Lille; 🇫🇷 Lille, France

Lorient Hospital; 🇫🇷 Lorient, France

UH La conception AP-HM; 🇫🇷 Marseille, France

UH Nantes; 🇫🇷 Nantes, France

Clinique Pierre Cherest; 🇫🇷 Neuilly-sur-Seine, France

UH Nîmes; 🇫🇷 Nîmes, France

Cochin Hospital, APHP; 🇫🇷 Paris, France

Hospital of Orléans; 🇫🇷 Orléans, France

Poissy Saint Germain en Laye Hospital; 🇫🇷 Poissy, France

UH Potiers; 🇫🇷 Potiers, France

Clinique Mutualiste de la Sagesse; 🇫🇷 Rennes, France

UH Toulouse; 🇫🇷 Toulouse, France

UH Strasbourg; 🇫🇷 Strasbourg, France

UH Rouen; 🇫🇷 Rouen, France

UH Rennes; 🇫🇷 Rennes, France

Polyclinique de L'Atlantique; 🇫🇷 Saint-Herblain, France

UH Pointe-à-Pitre; 🇬🇵 Pointe-à-Pitre, Guadeloupe/France, Guadeloupe

UHR Tours; 🇫🇷 Tours, France

UH Angers; 🇫🇷 Angers, France

Clinique Jules Verne; 🇫🇷 Nantes, France